Treating Apathy in Alzheimer's Disease Patients: A Meta-Analysis

Three studies evaluating methylphenidate and 1 evaluating modafinil had the primary objective of improving apathy at baseline.

A review published in the Cochrane Library aimed to assess the safety and efficacy of pharmacologic treatments for apathy in patients with Alzheimer's disease and other primary outcomes.

Study authors searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) portal, ICTRP databases for double-blind, randomized, placebo-controlled trials investigating apathy as a primary or secondary outcome in patients with Alzheimer's disease. They rated the overall quality of evidence for each outcome and calculated mean differences (MD) or risk ratios (RR) for all relevant outcome measures.

A total of 21 studies involving 6384 patients were included in the quantitative analyses. Three studies evaluating methylphenidate and 1 evaluating modafinil had a primary objective of improving apathy among patients who had clinically significant apathy at baseline.

Methylphenidate demonstrated an improvement in apathy vs placebo when measured by the apathy evaluation scale (MD -4.99, 95% CI: -9.55 to -0.43) but not when assessed with the neuropsychiatric inventory (NPI)-apathy subscale (MD -0.08, 95% CI: -3.85 to 3.69). In addition, methylphenidate showed possible improvement in cognition (MD 1.98, 95% CI: 1.06 to 2.91) and instrumental activities of daily living (MD 2.30, 95% CI: 0.74 to 3.86; P =.004) when compared with placebo. Regarding safety, the authors found no difference between methylphenidate and placebo in the risk of developing an adverse event (RR 1.28, 95% CI: 0.67 to 2.42).

Study authors found insufficient evidence to determine the effect of modafinil on apathy according to the FrSBe-apathy scale (MD 0.27, 95% CI: -3.51 to 4.05).

Other studies designated apathy as a secondary outcome and patients were not included on their apathy status at baseline. Evidence on cholinesterase inhibitors and their discontinuation, antipsychotics and their discontinuation, antidepressants, mibampator, valproate, and semagacestat were graded as low or very low quality.

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Based on the meta-analysis, the authors concluded methylphenidate may improve apathy, cognition, and functional performance in Alzheimer's disease patients (low quality evidence). "Additional studies should be encouraged targeting people with [Alzheimer's disease] with clinically significant apathy which investigate apathy as a primary outcome measure, and which have a longer duration and a larger sample size. This could increase the quality of evidence for methylphenidate, and may confirm whether or not it is an effective pharmacotherapy for apathy in [Alzheimer's disease]," concluded lead author Myuri T Ruthirakuhan.